Histone sequence variation in divergent eukaryotes facilitates diversity in chromatin packaging

Abstract

The histone proteins defining nucleosome structure are highly conserved in common model organisms and are frequently portrayed as uniform chromatin building blocks. We surveyed over 1700 complete eukaryotic genomes and confirm that almost all encode recognisable canonical core histones. Nevertheless, divergent eukaryotes show unrecognised diversity in histone sequences and offer an opportunity to observe the potential for nucleosome variation. Recombinant histones for Plasmodium falciparum, Giardia lamblia, Encephalitozoon cuniculi and Leishmania major were prepared alongside those for human, Xenopus laevis and Saccharomyces cerevisiae. All could be assembled into nucleosomes in vitro on sequences known to direct positioning with metazoan histones. P. falciparum histones refolded into very stable nucleosomes consistent with a highly regulated transcriptional programme. In contrast, G. lamblia and E. cuniculi histones formed less stable nucleosomes and were prone to aggregation as H3-H4 tetramers. Inspection of the histone fold dimer interface residues suggested a potential to form tetrasomal arrays consistent with polymerisation. DNA binding preferences observed using systematic evolution of ligands by exponential enrichment (SELEX) for human, P. falciparum and E. cuniculi histone octamers were highly similar and reflect a shared capability to package diverse genomic sequences. This demonstrates that nucleosomal organisation is retained across eukaryotes and can accommodate genome variation, but histone protein sequences vary more than commonly recognised to provide the potential for diversity of chromatin features.

Histone-organized chromatin in bacteria

“…Histones are among the most conserved and abundant proteins across eukaryotes (Postberg et al . 2010; Patwal et al . 2021; Soo and Warnecke 2021).…”

“…Histones are among the most conserved and abundant proteins across eukaryotes (Postberg et al 2010;Patwal et al 2021;Soo and Warnecke 2021). The 'histone fold' is composed of three alpha helices (connected by two short loops) and dimerizes in a head-totail 'handshake motif' (Arents et al 1991).…”

Viral histones: pickpocket’s prize or primordial progenitor?

“…A remarkable feature of the four core histones is that they are found in all eukaryotes [ 5 , 6 ] spanning at least 1.6–2.4 billion years of the diversification of modern eukaryotes [ 7 – 9 ], and are among the most conserved proteins known. The mean amino acid identities in the HFDs to human core histones across 1208 eukaryotic genomes are 91%, 83%, 92%, and 93% for H2A, H2B, H3, and H4 [ 10 ]. Despite this strong conservation, some histones in certain protists such as H2B in Encephalitozoon cunicul i can have as little as 24% identity with human H2B yet are still able to form nucleosomes that bind DNA with little sequence preference [ 10 ].…”

“…The mean amino acid identities in the HFDs to human core histones across 1208 eukaryotic genomes are 91%, 83%, 92%, and 93% for H2A, H2B, H3, and H4 [ 10 ]. Despite this strong conservation, some histones in certain protists such as H2B in Encephalitozoon cunicul i can have as little as 24% identity with human H2B yet are still able to form nucleosomes that bind DNA with little sequence preference [ 10 ]. In contrast to the general conservation of core histones, some histone variants, paralogs of the core histones, such as the centromere-specific H3 variant cenH3 and germline-restricted H2A variant H2A.B, have evolved rapidly and adapted for specialized functions [ 11 , 12 ].…”

Nucleosome Structures Built from Highly Divergent Histones: Parasites and Giant DNA Viruses

“…The four core histones share the typical eukaryotic features of histone-fold domains, containing three α helices separated by two loops [ 55 ]. Parasite histones generally have diverse amino acid sequences, with remarkably low sequence identity compared to metazoan histones [ 58 , 59 ]. Indeed, the identities of the Giardia lamblia ( G. lamblia ) histone-fold domains of H2A, H2B, H3, and H4 compared to the human histone-fold domains are 48, 49, 60, and 78%, respectively.…”